Repaglinide Trimethoprim

REPAGLINIDE TRIMETHOPRIM t repaglinide levels (by approximately 40%) risk of hypoglycaemia Hepatic metabolism inhibited Manufacturers do not recommend concurrent use... 

CYP2C8 and CYP3A4 are involved in the metabolism of repaglinide (68). Trimethoprim is a selective inhibitor of CYP2C8. When nine healthy volunteers aged 19-23 years, 8 men) took placebo or trimethoprim 160 mg bd for 3 days followed by 0.25 mg of repaglinide 1 hour after the last dose of trimethoprim, the AUC of repaglinide increased by 61% and the Cmax increased by 41% compared with placebo. 

Neimi M, Kajosaari LI, Neuvonen M, Backman JT, Neuvonen PJ. The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects. Br J Clin Pharmacol 2004 57 441-7. 

Trimethoprim increases the AUC of repaglinide and would be expected to increase its effects in some patients. The effect of trimethoprim on the AUC of rosiglitazone is more modest and less likely to be clinically relevant. Trimethoprim does not appear to significantly affect the pharmacokinetics of intravenous tolbutamide. 

In a study in 9 healthy subjects trimethoprim 160 mg twice daily for 3 days increased the AUC and the maximum plasma level of a single 250-microgram dose of repaglinide by 61% and 41%, respectively. However, the blood glucose-lowering effect of repaglinide was unchanged. ... 

Repaglinide is mainly metabolized by CYP2C8 and CYP3A4. Trimethoprim... 

Roustit M, Blondel E, Villier C, Fonrose X, Mallaret MP. Symptomatic hypoglycaemia associated with trimethoprim/sulfamethoxa-zole and repaglinide in a diabetic patient. Ann Pharmacother 2010 44 764—7. 

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